Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling

被引：13
作者：
Abdullah, Ahmad [1 ]
Herdenberg, Carl [1 ]
Hedman, Hakan [1 ,2 ]
机构：
[1] Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden
[2] NUS M31, Oncol Res Lab, S-90185 Umea, Sweden
来源：
SCIENTIFIC REPORTS | 2021年 / 11卷 / 01期
关键词：
COLORECTAL-CANCER; RECEPTOR; CELLS; DIFFERENTIATION; IDENTIFICATION; ACTIVATION; EXPRESSION; NEOGENIN; PATHWAY; BOVINE;
D O I：
10.1038/s41598-021-87949-7
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.
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页数：12
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